We will utilize the radioactive microsphere technique in the intact dog heart with regional myocardial ischemia to demonstrate drug effects on blood flow distribution between endocardium and epicardium of normal and ischemic areas of the left ventricle. Certain indices which have been previously developed in ours and other laboratories will be used to predict changes in transmural blood flow based on drug-induced hemodynamic changes. Studies will be performed with beta adrenergic blocking agents, dipyridamole, sodium nitroprusside, nitroglycerin and nifedipine to determine mechanisms by which these agents alter regional myocardial blood flow. The determinants of oxygen balance and substrate utilization will be studied in the regionally ischemic myocardium and in the isolated ischemic gracilis muscle preparation in the presence and absence of drug intervention. The effects of nitroglycerin and ortho-iodo sodium benzoate will be evaluated to determine if an acute decrease in the affinity of hemoglobin for oxygen (higher P-50) can provide utilizable oxygen to the ischemic tissue which results in improved mechanical performance. Chronic experiments will be performed in unanesthetized dogs to determine if propranolol or myocardial infarction can produce increases in P-50 as has been reported in man.